Factor VII, which is involved in the clotting cascade, has proven to be a useful therapeutic agent to treat a variety of pathological conditions. Accordingly, there is an increasing need for formulations comprising activated factor VII polypeptides that are pharmaceutically acceptable and exhibit a uniform and predetermined clinical efficacy.
During the commercial manufacture of factor VII polypeptides, avoiding the formation of aggregates such as di- and oligomers of the polypeptide of interest is a challenge. Such product-related impurities are unwanted because of their potential antigenicity. Typically, extremes of pH and high temperatures are avoided in order to control the formation of aggregates/dimers during production.
WO 2007/026020 A1 concerns a method of purifying a composition comprising factor VII and factor VIIa polypeptides of production biproducts, whilst minimising the concurrent formation of factor VII or factor VIIa auto-degradation products.
Hence, in connection with the manufacture of factor VII polypeptides, there is a need for a production step by which the presence of dimers (including higher oligomers) of the factor VII polypeptide is reduced without any significant loss of yield. This will result in a safer and more stable drug substance and eventually a safer and more stable drug product.